Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies

Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (...

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Main Authors: Ying Zhang, Yan Ma, Yu-Ke Ji, Yi-Fei Jiang, Duo Li, Wan Mu, Mu-Di Yao, Jin Yao, Biao Yan
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-024-02013-x
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Summary:Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are emerging as novel gene regulators, involved in various biological processes and human diseases. In this study, tsRNA-Gln-i-0095 was identified as a novel regulator, which was significantly upregulated in retinal ischemia/reperfusion (I/R) injury. Reducing the levels of tsRNA-Gln-i-0095 suppressed reactive gliosis, lowered inflammatory cytokine levels, and protected retinal ganglion cells from I/R injury. These effects led to reduced structural and functional damage, inhibited glial activation and inflammation, and enhanced neuronal function. Mechanistically, tsRNA-Gln-i-0095 downregulated the expression of NFIA and TGFBR2 through a miRNA-like mechanism. Collectively, this study highlights the potential of targeting tsRNA-Gln-i-0095 as a novel therapeutic approach to reduce retinal I/R injury and preserve visual function. Graphical abstract
ISSN:1478-811X